tbuckley/cabot-search huggingface dataset:
Dose-response assessment of cerebral P-glycoprotein inhibition in vivo with [18F]MC225 and PET
Authors: Lara Garcia-Varela, Pascalle Mossel, Pablo Aguiar, Daniel A. Vazquez-Matias, Aren van Waarde, Antoon T.M. Willemsen, Anna L. Bartels, Nicola A. Colabufo, Rudi A.J.O. Dierckx, Philip H. Elsinga, Gert Luurtsema
Journal: Journal of Controlled Release (2022)

The Blood-Brain Barrier P-glycoprotein (P-gp) function can be altered in several neurodegenerative diseases and due to the administration of different drugs which may cause alterations in drug concentrations and consequently lead to a reduced effectiveness or increased side-effects. The novel PET radiotracer [18F]MC225 is a weak P-gp substrate that may show higher sensitivity to detect small changes in P-gp function than previously developed radiotracers. This study explores the sensitivity of [18F]MC225 to measure the dose-dependent effect of P-gp inhibitor tariquidar. Twenty-three rats were intravenously injected with different doses of tariquidar ranging from 0.75 to 12 mg/kg, 30-min before the dynamic [18F]MC225-PET acquisition with arterial sampling. Tissue and blood data were fitted to a 1-Tissue-Compartment-Model to obtain influx constant K1 and distribution volume VT, which allow the estimation of P-gp function. ANOVA and post-hoc analyses of K1 values showed significant differences between controls and groups with tariquidar doses >3 mg/kg; while applying VT the analyses showed significant differences between controls and groups with tariquidar doses >6 mg/kg. Dose-response curves were fitted using different models. The four-parameter logistic sigmoidal curve provided the best fit for K1 and VT data. Half-maximal inhibitory doses (ID50) were 2.23 mg/kg (95%CI: 1.669-2.783) and 2.93 mg/kg (95%CI: 1.135-3.651), calculated with K1 or VT values respectively. According to the dose-response fit, differences in [18F]MC225-K1 values could be detected at tariquidar doses ranging from 1.37 to 3.25 mg/kg. Our findings showed that small changes in the P-gp function, caused by low doses of tariquidar, could be detected by [18F]MC225-K1 values, which confirms the high sensitivity of the radiotracer. The results suggest that [18F]MC225 may allow the quantification of moderate P-gp impairments, which may allow the detection of P-gp dysfunctions at the early stages of a disease and potential transporter-mediated drug-drug interactions.
Association of a Callback Program With Emergency Department Revisit Rates Among Patients Seeking Emergency Care
Authors: Scott Fruhan, Corey B. Bills
Journal: JAMA Network Open (2022)

The emergency department (ED) discharge process often involves haste and poor communication.To assess the association of an automated telephone call 2 days after ED discharge with the likelihood of an unplanned ED revisit at both 72 hours and 7 days after the index visit and with perceived care metrics measured at 14 days.This prospective nonrandomized clinical trial was conducted at a single academically affiliated county emergency department among 8110 patients presenting to and discharged from the ED during a 10-week period from June 25 to August 30, 2018. Initial statistical analysis was performed from February 1 to November 30, 2020, with additional analyses performed from March 1 to 16, 2022.Participants were allocated in a nonrandom fashion to 1 of 2 groups: patients who received an automated telephone call 2 days after discharge were compared with patients who received no call 2 days after discharge. All patients received a telephone questionnaire at 14 days to assess secondary outcome measures.The primary outcome was a return visit to the ED at 7 days. Secondary outcomes included a return visit to the ED within 72 hours, a return visit to the ED within 7 days resulting in hospital admission, and patient-reported perceptions of their care measured by 4 questions related to quality metrics assessed at 14 days. A secondary analysis compared patients who actually responded to the initial call at 2 days with all nonresponders, regardless of whether they received a call. Analyses were made on an intention-to-treat basis.More than 15 000 patients were seen in the ED during the 10-week study period, and 10 948 were discharged. A total of 8110 patient encounters (4460 male patients [55.0%]; 3313 Hispanic patients [40.9%]; mean [SD] age, 40.5 [19.4] years) were enrolled. A total of 2958 patients (36.5%) received an automated telephone call at 2 days after discharge, while 5152 (63.5%) received no call. Rates of ED return within 7 days of the initial index visit were significantly lower among those who received a call at 2 days than those who did not receive a call (224 of 2958 [7.6%] vs 533 of 5152 [10.3%]; P < .001). Patients who received a 2-day call were more likely than those who did not receive a call to have followed up with a health care clinician (67.9% [374 of 551] vs 66.3% [604 of 911]), understood their health issues (77.5% [490 of 632] vs 74.9% [780 of 1042]), and have received their discharge medications (87.0% [507 of 583] vs 83.6% [793 of 949]), although none of these differences between the 2 groups were statistically significant.A telephone call to patients 2 days after discharge from the ED was associated with decreased ED use at 7 days after the index visit and may have been associated with marginal improvements in measured quality of care metrics.
Risk of SARS-CoV-2 Breakthrough Infection in Vaccinated Cancer Patients: A Retrospective Cohort Study
Authors: Anthony Rooney, Cory Bivona, Ben Liu, David Streeter, Han Gong, Qamar Khan
Journal: Journal of Hematology & Oncology (2022)

Although messenger RNA (mRNA) vaccines have established efficacy for prevention of severe SARS-CoV2 infection in the general population, their effectiveness in patients with malignancy, especially those on anti-neoplastic therapies, remains an area of open research. In order to better understand the risk of developing breakthrough SARS-CoV-2 infection and the outcomes associated with breakthrough infection for cancer patients, individual patient data from a curated outcomes database at the University of Kansas were retrospectively reviewed to determine the rate of breakthrough infection during an 8-month period encompassing the height of the delta variant surge. Although the rate of breakthrough infection in cancer patients after two doses of an mRNA vaccine remained low at 1.1%, hospitalization and death rates were 27 and 5%, respectively. Patients with hematologic malignancies, especially multiple myeloma, and those on anti-neoplastic therapy at the time of vaccination were found to be at higher risk for developing breakthrough infection.
The long noncoding RNA Malat1 regulates CD8+ T cell differentiation by mediating epigenetic repression
Authors: Jad N. Kanbar, Shengyun Ma, Eleanor S. Kim, Nadia S. Kurd, Matthew S. Tsai, Tiffani Tysl, Christella E. Widjaja, Abigail E. Limary, Brian Yee, Zhaoren He, Yajing Hao, Xiang-Dong Fu, Gene W. Yeo, Wendy J. Huang, John T. Chang
Journal: The Journal of Experimental Medicine (2022)

During an immune response to microbial infection, CD8+ T cells give rise to short-lived effector cells and memory cells that provide sustained protection. Although the transcriptional programs regulating CD8+ T cell differentiation have been extensively characterized, the role of long noncoding RNAs (lncRNAs) in this process remains poorly understood. Using a functional genetic knockdown screen, we identified the lncRNA Malat1 as a regulator of terminal effector cells and the terminal effector memory (t-TEM) circulating memory subset. Evaluation of chromatin-enriched lncRNAs revealed that Malat1 grouped with trans lncRNAs that exhibit increased RNA interactions at gene promoters and gene bodies. Moreover, we observed that Malat1 was associated with increased H3K27me3 deposition at a number of memory cell-associated genes through a direct interaction with Ezh2, thereby promoting terminal effector and t-TEM cell differentiation. Our findings suggest an important functional role of Malat1 in regulating CD8+ T cell differentiation and broaden the knowledge base of lncRNAs in CD8+ T cell biology.
Bioengineered 3D Living Fibers as In Vitro Human Tissue Models of Tendon Physiology and Pathology
Authors: Isabel Calejo, Claudia J. Labrador‐Rached, Manuel Gomez‐Florit, Denitsa Docheva, Rui L. Reis, Rui M. A. Domingues, Manuela E. Gomes
Journal: Advanced Healthcare Materials (2022)

Abstract Clinically relevant in vitro models of human tissue's health and disease are urgently needed for a better understanding of biological mechanisms essential for the development of novel therapies. Herein, physiological (healthy) and pathological (disease) tendon states are bioengineered by coupling the biological signaling of platelet lysate components with controlled 3D architectures of electrospun microfibers to drive the fate of human tendon cells in different composite living fibers (CLFs). In the CLFs‐healthy model, tendon cells adopt a high cytoskeleton alignment and elongation, express tendon‐related markers (scleraxis, tenomodulin, and mohawk) and deposit a dense tenogenic matrix. In contrast, cell crowding with low preferential orientation, high matrix deposition, and phenotypic drift leading to increased expression of nontendon related and fibrotic markers, are characteristics of the CLFs‐diseased model. This diseased‐like profile, also reflected in the increase of COL3/COL1 ratio, is further evident by the imbalance between matrix remodeling and degradation effectors, characteristic of tendinopathy. In summary, microengineered 3D in vitro models of human tendon healthy and diseased states are successfully fabricated. Most importantly, these innovative and versatile microphysiological models offer major advantages over currently used systems, holding promise for drugs screening and development of new therapies.
RELIght: A two‐year REal‐LIfe study of mepolizumab in patients with severe eosinophilic asTHma in Greece: Evaluating the multiple components of response
Authors: Maria Kallieri, Eleftherios Zervas, Evangelia Fouka, Konstantinos Porpodis, Marija Hadji Mitrova, Eleni Tzortzaki, Michael Makris, Maria Ntakoula, Andriana I. Papaioannou, Panagiotis Lyberopoulos, Katerina Dimakou, Sofia Koukidou, Sevasti Ampelioti, Anastasia Papaporfyriou, Konstantinos Katsoulis, Maria Kipourou, Nikoletta Rovina, Katerina Antoniou, Stylianos Vittorakis, Petros Bakakos, Paschalis Steiropoulos, Katerina Markopoulou, Panteleimon Avarlis, Ιlias C. Papanikolaou, Miltiadis Markatos, Eleni Gaki, Konstantinos Samitas, Konstantinos Glynos, Spyros A. Papiris, Despoina Papakosta, Nikolaos Tzanakis, Mina Gaga, Konstantinos Kostikas, Stelios Loukides
Journal: Allergy (2022)

Appendix S1 Table S1-S4 Fig S1-S4 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Excess Mortality in Massachusetts During the Delta and Omicron Waves of COVID-19
Authors: Jeremy Samuel Faust, Chengan Du, Chenxue Liang, Katherine Dickerson Mayes, Benjamin Renton, Kristen Panthagani, Harlan M. Krumholz
Journal: JAMA (2022)

Characteristics and Outcomes of Hospitalized Patients in South Africa During the COVID-19 Omicron Wave
Carcinoid Heart Disease
Authors: Raj K. Dangol, Marsiyana M. Henricus
Journal: New England Journal of Medicine (2022)

A 67-year-old man presented with a 1-month history of dyspnea and diarrhea. Thickened, stiff tricuspid-valve leaflets and tricuspid regurgitation were seen on transthoracic echocardiography (shown in videos), and abdominal imaging showed liver masses.
Post-discharge morbidity and mortality in children admitted with severe anaemia and other health conditions in malaria-endemic settings in Africa: a systematic review and meta-analysis
Authors: Titus K Kwambai, Amani T Mori, Sarah Nevitt, Anna Maria van Eijk, Aaron M Samuels, Bjarne Robberstad, Kamija S Phiri, Feiko O ter Kuile
Journal: The Lancet Child & Adolescent Health (2022)
Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis
Authors: María Crespo, Ivana Nikolic, Alfonso Mora, Elena Rodríguez, Luis Leiva‐Vega, Aránzazu Pintor‐Chocano, Daniel Horrillo, Lourdes Hernández‐Cosido, Jorge L. Torres, Eva Novoa, Rubén Nogueiras, Gema Medina‐Gómez, Miguel Marcos, Magdalena Leiva, Guadalupe Sabio
Journal: Hepatology (2022)

Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low-grade inflammation that contributes to the development of diabetes, steatosis, and insulin resistance. Recent research has shown that this chronic inflammation is crucially dependent on p38 pathway activity in macrophages, suggesting p38 inhibition as a possible treatment for obesity comorbidities. Nevertheless, we report here that lack of p38 activation in myeloid cells worsens high-fat diet-induced obesity, diabetes, and steatosis. Deficient p38 activation increases macrophage IL-12 production, leading to inhibition of hepatic FGF21 and reduction of thermogenesis in the brown fat. The implication of FGF21 in the phenotype was confirmed by its specific deletion in hepatocytes. We also found that IL-12 correlates with liver damage in human biopsies, indicating the translational potential of our results. Our findings suggest that myeloid p38 has a dual role in inflammation and that drugs targeting IL-12 might improve the homeostatic regulation of energy balance in response to metabolic stress.
Targeting the low detector with artificial intelligence
Authors: Cesare Hassan, Alessandro Repici
Journal: Endoscopy (2022)

Colorectal neoplasia was not meant to be detected by human endoscopists. Disappointingly, one in every three polyps is missed by an expert endoscopist. When assuming an average adenoma detection rate (ADR) of 30 %, this indicates that for every patient correctly diagnosed there is one polyp that has been missed. This is further worsened by an additional inter-endoscopist variability exemplified by a threefold difference between high and low detectors, suggesting that low detectors can miss more than two polyps out of three, which is clearly unacceptable from clinical, technical, and ethical standpoints.
Symptom‐Based Cluster Analysis Categorizes Sjögren's Disease Subtypes: An International Cohort Study Highlighting Disease Severity and Treatment Discordance
Authors: Sara S. McCoy, Miguel Woodham, Christie M. Bartels, Ian J. Saldanha, Vatinee Y. Bunya, Noah Maerz, Esen K. Akpek, Matthew A. Makara, Alan N. Baer
Journal: Arthritis & Rheumatology (2022)

Although symptom relief is a critical aspect for successful drug development in Sjögren's disease, patient experiences with Sjögren's-related symptoms are understudied. Our objective was to determine how pain, dryness, and fatigue, the cardinal symptoms of Sjögren's disease, drive cluster phenotypes. We used data from the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry and a Sjögren's Foundation survey. We performed hierarchical clustering of symptoms by levels of dryness, fatigue, and pain. Using international and US cohorts, we performed multiple logistic regression analysis to compare the clusters, which included comparisons of differences in symptoms, quality of life (QoL), medication use, and systemic manifestations. Four similar clusters were identified among 1,454 SICCA registrants and 2,920 Sjögren's Foundation survey participants: 1) low symptom burden in all categories (LSB); 2) dry with low pain and low fatigue (DLP); 3) dry with high pain and low to moderate fatigue (DHP); and 4) high symptom burden in all categories (HSB). Distribution of SICCA registrants matching the symptom profile for each cluster was 10% in the LSB cluster, 30% in the DLP cluster, 23% in the DHP cluster, and 37% in the HSB cluster. Distribution of survey participants matching the symptom profile for each cluster was 23% in the LSB cluster, 14% in the DLP cluster, 21% in the DHP cluster, and 42% in the HSB cluster. Individuals in the HSB cluster had more total symptoms and lower QoL but lower disease severity than those in the other clusters. Despite having milder disease as measured by laboratory tests and organ involvement, individuals in the HSB cluster received immunomodulatory treatment most often. We identified 4 symptom-based Sjögren's clusters and showed that symptom burden and immunomodulatory medication use do not correlate with Sjögren's end-organ or laboratory abnormalities. Findings highlight a discordance between objective measures and treatments and offer updates to proposed symptom-based clustering approaches.
Electrical charge on ferroelectric nanocomposite membranes enhances SHED neural differentiation
Authors: Xiaochan Li, Boon Chin Heng, Yunyang Bai, Qianqian Wang, Min Gao, Ying He, Xinwen Zhang, Xuliang Deng, Xuehui Zhang
Journal: Bioactive Materials (2022)

Stem cells from human exfoliated deciduous teeth (SHED) uniquely exhibit high proliferative and neurogenic potential. Charged biomaterials have been demonstrated to promote neural differentiation of stem cells, but the dose-response effect of electrical stimuli from these materials on neural differentiation of SHED remains to be elucidated. Here, by utilizing different annealing temperatures prior to corona poling treatment, BaTiO3/P(VDF-TrFE) ferroelectric nanocomposite membranes with varying charge polarization intensity (d33 ≈ 0, 4, 12 and 19 pC N-1) were fabricated. Enhanced expression of neural markers, increased cell elongation and more prominent neurite outgrowths were observed with increasing surface charge of the nanocomposite membrane indicating a dose-response effect of surface electrical charge on SHED neural differentiation. Further investigations of the underlying molecular mechanisms revealed that intracellular calcium influx, focal adhesion formation, FAK-ERK mechanosensing pathway and neurogenic-related ErbB signaling pathway were implicated in the enhancement of SHED neural differentiation by surface electrical charge. Hence, this study confirms the dose-response effect of biomaterial surface charge on SHED neural differentiation and provides preliminary insights into the molecular mechanisms and signaling pathways involved.
Central nervous system infections in solid organ transplant recipients: Results from the Swiss Transplant Cohort Study
Authors: Lorena van den Bogaart, Brian M. Lang, Simona Rossi, Dionysios Neofytos, Laura N. Walti, Nina Khanna, Nicolas J. Mueller, Katia Boggian, Christian Garzoni, Matteo Mombelli, Oriol Manuel
Journal: Journal of Infection (2022)

To describe the epidemiology and clinical presentation of central nervous system (CNS) infections in solid organ transplant (SOT) recipients in the current era of transplantation.Patients from the Swiss Transplant Cohort Study (STCS) transplanted between 2008 and 2018 were included with a median follow-up of 3.8 years. Epidemiological, microbiological, and clinical data were extracted from the STCS database and patients' medical records. We calculated incidence rates and 90-day survival of transplant recipients with CNS infection.Among 4762 patients, 42 episodes of CNS infection in 41 (0.8%) SOT recipients were identified, with an overall incidence rate of 2.06 per 1000 patient-years. Incidence of CNS infections was similar across all types of transplantations. Time to CNS infection onset ranged from 0.6 to 97 months after transplant. There were 22/42 (52.4%) cases of viral infections, 11/42 (26.2%) of fungal infections, 5/42 (11.9%) of bacterial infections and 4/42 (9.5%) of probable viral/bacterial etiology. Clinical presentation was meningitis/encephalitis in 25 cases (59.5%) and brain-space occupying lesions in 17 cases (40.5%). Twenty-three cases (60.5%) were considered opportunistic infections. Diagnosis were achieved mainly by brain biopsy/necropsy (15/42, 36%) or by cerebrospinal fluid analysis (20/42, 48%). Up to 40% of cases (17/42) had concurrent extra-neurological disease localizations. Overall, 90-day mortality rate was 29.0% (73.0% for fungal, 14.0% for viral and 11.0% for bacterial and probable infections, p<0.0001).CNS infections were rare in the STCS, with viral meningoencephalitis being the most common disease. Fungal infections were associated with a high mortality.
Prehospital interventions and neurological outcomes in marathon-related sudden cardiac arrest using a rapid mobile automated external defibrillator system in Japan: a prospective observational study
Authors: Hideharu Tanaka, Tomoya Kinoshi, Shota Tanaka, Ryo Sagisaka, Hiroyuki Takahashi, Etsuko Sone, Takahiro Hara, Yui Takeda, Hiroshi Takyu
Journal: British Journal of Sports Medicine (2022)

To describe neurological outcomes after sudden cardiac arrests (SCAs) in road and long-distance races using a rapid mobile automated external defibrillator system (RMAEDS) intervention.
Lung transplantation in HIV-positive patients: a European retrospective cohort study
Authors: Claire Rouzaud, Cristina Berastegui, Clément Picard, Robin Vos, Laurent Savale, Xavier Demant, Alessandro Bertani, Erik Verschuuren, Peter Jaksch, Anna Reed, Letizia Corinna Morlacchi, Martine Reynaud-Gaubert, Olivier Lortholary, Elie Fadel, Marc Humbert, Jens Gottlieb, Jérôme Le Pavec
Journal: European Respiratory Journal (2022)

<b>In selected HIV-positive patients, lung transplantation provided good transplant and patient survivals, without more infections than reported in HIV-negative patients. Further work is needed to determine the best immunosuppressive regimens.</b>https://bit.ly/3kyLnDL
Systematic Review and Meta-Analysis to Identify the Immunocytochemical Markers Effective in Delineating Benign from Malignant Thyroid Lesions in FNAC Samples
Authors: Uma Mohan, Sumsum P. Sunny, Pramila Mendonca, Moni A. Kuriakose, Subramanian Kannan, Amritha Suresh
Journal: Endocrine Pathology (2022)
Moyamoya disease: diagnosis and interventions
Authors: Masafumi Ihara, Yumi Yamamoto, Yorito Hattori, Wanyang Liu, Hatasu Kobayashi, Hiroyuki Ishiyama, Takeshi Yoshimoto, Satoru Miyawaki, Tim Clausen, Oh Young Bang, Gary K Steinberg, Elisabeth Tournier-Lasserve, Akio Koizumi
Journal: The Lancet Neurology (2022)